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Biomedical subjects

K L Khanduja

Publications and source records attributed to K L Khanduja.

At least 19 recordsLinked to original sources
PubMed1999

Effect of 50 Hz sinusoidal electromagnetic field on the kinetics of 14CO2 exhalation after [14C]-N-nitrosodiethylamine administration in mice.

N-Nitrosodiethylamine (NDEA) has been identified as a typical environmental carcinogen. Its metabolism was studied in mice under the influence of an electromagnetic field (EMF). After intraperitoneal administration of [14C]-NDEA, 0.2 microCi/100 g body weight resulted in 22.8% of the total radioactivity exhaled as 14CO2 within 1 h. Mice were exposed to a 50 Hz, 2 mT (rms) electromagnetic field, 8 h/day for 8 weeks. There was a significant increase in the metabolic turnover of [14C]-NDEA into 14CO2 at the end of both 6 and 8 weeks of field exposure, i.e., 26.9% and 37.4% respectively. The enhanced capacity of mice to metabolize NDEA after the exposure to EMF may result in animals with a smaller amount of the bioactive carcinogen burden, thereby indicating a protective role of 2 mT EMF in a whole animal study.

Animals↗
PubMed1999

Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice.

The polyphenolic antioxidants, consumed as an integral part of vegetables, fruits and beverages, are suggested as possessing anticarcinogenic properties. In the present study we have looked into the anticarcinogenic potential of plant polyphenols ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin.

Animals↗
PubMed1998

Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients.

The ability of monoclonal antibodies (MAb) against a human B lymphocyte alloantigen has been suggested to discriminate between rheumatic fever "susceptible" individuals and persons with a lower risk of developing RF. However, while such MAb have been reported to identify a majority of RF/RHD patients in some populations, a reduced discriminatory ability has been observed in others. Antigenic variation in the RF marker(s) may exist among ethnic groups which reduce the discriminatory ability of these monoclonal antibodies. We developed MAb using B lymphocytes from RF patients of North Indian ethnic origin. In this same population we compared the new MAb (PGI/MN II) with a previously described MAb of Caucasian ethnic origin (D8/17). In three groups: acute rheumatic fever patients (no evidence of previous attacks of rheumatic fever), patients with chronic rheumatic heart disease and normal controls from the same population, we found a greater discriminating ability of PGI/MNII MAb to identify Indian RF/RHD patients than with the D8/17 MAb. Further, sixty percent of 142 siblings of the RF/RHD patients were "positive" when tested with PGI/MN II. The data from these studies suggest that before such MAb can be used for identification of RF "susceptibles" in public health programs, variation among ethnic populations must be assessed.

Adolescent↗
PubMed1998

Polyphenols inhibit promotional phase of tumorigenesis: relevance of superoxide radicals.

Ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA) offer considerable promise as anticarcinogens. The role of these dietary polyphenols was investigated in the promotional phase of carcinogenesis. Topical application of polyphenols simultaneously with phorbol-12-myristate-13-acetate (PMA) or mezerein resulted in significant protection against 7,12-dimethyl-benz[a]anthracene-induced skin tumors in mice. Caffeic acid was the most effective inhibitor of tumor promotion. In vivo and in vitro treatment of murine peritoneal macrophages with the tumor promoters resulted in stimulation of superoxide anion radical formation. Tannic acid, caffeic acid, and ferulic acid were stronger inhibitors of PMA- and mezerein-induced superoxide anion radical than ellagic acid in in vivo and in vitro conditions. Treatment of [1(3)-14C]glycerol- or [methyl-14C]choline chloride-labeled resident or thioglycollate-elicited macrophages with PMA and mezerein led to accumulation of radioactive diacylglycerol equivalents. The polyphenols were capable of inhibiting these releases.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Changes in rat alveolar macrophageal antioxidant defense and reactive oxygen species release by high dietary vitamin E.

For the past decade there has been emphasis on the immunomodulatory effects of vitamin E apart from its established role as a free radical scavenger. In alveolar macrophages (AMs), the role of vitamin E supplementation has not yet been investigated sufficiently. In the present study we have evaluated the effects of high vitamin E (DL-alpha-tocopheryl acetate, alpha-TA) supplementation for 10 d on rat-alveolar macrophageal antioxidant defense and reactive oxygen species (ROS) release. There was an increase in plasma vitamin E content from 5.22 +/- 1.30, at 50 mg to 12.23 +/- 1.06 and 22.32 +/- 2.02 micrograms/mL at 250 and 1,250 mg alpha-TA/kg dietary supplementation. Alveolar macrophage-vitamin E content enhanced by 56 to 75% at 250 and 1,250 mg alpha-TA diet as compared with control diet. Superoxide dismutase activity decreased and catalase and glutathione peroxidase activities increased significantly in AMs of 250 and 1,250 mg alpha-TA diet-fed rats. Reduced glutathione, total glutathione, and glutathione-S-transferase activity in AMs did not change significantly at any of the high doses of alpha-TA supplementation. On stimulation of AMs by phorbol-12-myristate-13-acetate (PMA), there was 2.8- and 3.5-fold enhancement in superoxide (O2-.) and H2O2 production, respectively, at 50 mg alpha-TA dose. But this increase by PMA could not take place in AMs from animals supplemented with 250 and 1,250 mg alpha-TA. It may therefore be concluded that high alpha-TA supplementation in diet may equip the AMs with a stronger defense against oxygen-free radical mediated damage to them.

Albuminuria↗
PubMed1998

Geriforte stimulates antioxidant defense system.

Geriforte, a herbomineral preparation, feeding at 1 g% dose level for 4 weeks significantly increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in liver of mice. In rats, in addition to these enzymes, the levels of reduced glutathione (GSH) were also significantly enhanced. However, only SOD in mice and, CAT and SOD activities in rat lung were significantly elevated after Geriforte treatment. A decrease in superoxide (O2-) and H2O2 release by alveolar macrophages obtained from rats fed on Geriforte containing diet was observed. The results suggest that Geriforte feeding stimulates antioxidant defense system and indicate the future preventive/therapeutic prospects of this preparation against free radical damage under various pathological states.

Animals↗
PubMed1997

Reactive oxygen species formation in peripheral blood neutrophils in different types of smokers.

The present study was envisaged to assess the state of oxidative metabolism of neutrophils, recovered from smokers (cigarette, beedi, hookah and mixed products) and non-smokers. Superoxide anion (O2.-) production was significantly higher in neutrophils from all groups of smokers (P < 0.001). Total leukocyte count (TLC) was significantly more in symptomatic subjects among the cigarette, hookah and mixed smokers (P < 0.05). Total neutrophil count (TNC) was significantly higher in symptomatic than asymptomatic subjects of hookah and mixed smoking groups (P < 0.05). In the pathogenesis of chronic obstructive pulmonary disease (COPD) in tobacco smokers, the role of leukocytosis, increased neutrophil sequestration into the lung, increased neutrophil toxic oxygen species including superoxide release in the lung may cause direct injury to lung tissues.

Adult↗
PubMed1994

Influence of combined deficiency of fat and vitamin A on benzo(a)pyrene-induced lung carcinogenesis in rats.

The present study shows the effect of combined dietary deprivation of fat and vitamin A on benzo(a)pyrene (BaP) induced lung carcinogenesis in male Wistar rats. Lung tumors were induced by intratracheal instillation of BaP-Fe2O3 in normal saline. The tumor incidence and tumor burden in control animals were 82% and 2.28 respectively. Fat deficiency decreased the tumor incidence to 57% and tumor burden to 1.66. On the other hand, in vitamin A deficiency these were 83% and 4.02 respectively. Fat deprivation in the diet of animals fed with vitamin A deficient diet decreased the tumor incidence and tumor burden to 69.6% and 2.7 respectively. The results suggest a protective role of low intake of fat in vitamin A deficiency for BaP-induced lung tumorigenesis in rats.

Animals↗
PubMed1993

Serum beta-N-acetylhexosaminidase, carcinoembryonic antigen & sialic acid in benign & malignant extrahepatic biliary obstruction.

Study of tumour markers to differentiate benign and malignant extra hepatic biliary obstructions showed that levels fo serum beta-N-acetylhexosaminidase and lipid associated sialic acid were not different in the two groups. The levels of carcinoembryonic antigen (CEA) and total sialic acid (TSA), on the other hand, were significantly higher in patients with the malignant biliary obstruction. At a cut-off value of 6.4 ng/ml (mean + 2SD) CEA had 66.7 per cent true positivity in malignancy 100 per cent true negativity in control and 78 per cent true negativity in the benign group. Similarly, TSA at a cut off value of 60 mg/dl had 61 per cent true positivity in malignancy, 90 per cent true negativity in controls and 70 per cent true negativity in the benign group. These two tumour markers appear to have similar diagnostic potential for malignant extrahepatic biliary obstruction. Surgical management of the malignant obstruction did not result in a decline in the elevated levels of these two markers during the post-surgical period of 7 days.

Bile Duct Neoplasms↗
PubMed1992

Effect of combined deficiency of fat and vitamin A on N-nitrosodiethylamine-induced lung carcinogenesis in mice.

The present investigation shows the effect of combined dietary deprivation of fat and vitamin A on N-nitrosodiethylamine (NDEA) induced lung carcinogenesis in male Swiss NMRI mice. Lung tumors were induced by three intragastric administrations of NDEA (80, 80, 40, mg/kg body wt.) in normal saline with a gap of 4 weeks between each administration. The tumor incidence and tumor burden in control animals were found to be 39.1 and 3.9%, respectively. Fat deficiency decreased the tumor incidence to 30.4% and tumor burden to 3.7%. On the other hand, vitamin A deficiency increased them to 95.6 and 6.8%, respectively. Fat deprivation in the diet of animals fed with vitamin A deficient diet decreased the tumor burden and tumor incidence to 59.0 and 4.0%, respectively which were still more than in the control animals. This study suggests a protective role for low intake of fat in vitamin A deficiency.

Animals↗
PubMed1991

Influence of ellagic acid on antioxidant defense system and lipid peroxidation in mice.

Addition of ellagic acid (EA) to liver microsomes of mice resulted in a steady increase in inhibition of NADPH-dependent lipid peroxidation up to 2 mM concentration. The maximum of 70% inhibition of ascorbate-dependent lipid peroxidation was achieved at 1 mM concentration of EA. Feeding of EA significantly increased the levels of reduced glutathione and glutathione reductase in liver and lungs of male and female mice. However, there were no changes in the activities of catalase and superoxide dismutase. On the other hand, microsomes from liver and lungs of EA fed animals showed significantly suppressed NADPH- and ascorbate-dependent lipid peroxidation.

Animals↗
PubMed1990

Effect of cigarette smoke inhalation on benzo[a]pyrene-induced lung carcinogenesis in vitamin A deficiency in the rat.

Vitamin A deficiency caused a significant increase (P less than 0.05) in benzo[a]pyrene (BP)-induced lung tumor incidence and tumor burden in male Wistar rats. Inhalation of cigarette smoke during initiation and post-initiation phases of carcinogenesis resulted in higher tumor burden as compared to the same observed in the animals exposed to cigarette smoke during the post-initiation phase only. Stimulation in tumor burden by cigarette smoke was increased further by vitamin A deficiency.

Administration, Inhalation↗
PubMed1990

Differential effects of fat deficiency on hepatic and pulmonary drug metabolizing enzymes in rat and mouse.

In the present study, we have evaluated the effect of dietary fat deprivation on the carcinogen/drug metabolizing enzymes in rats and mice. In rats, hepatic AHH, Cyt.P-450 Cyt.b5 and Cyt.c-reductase were significantly decreased due to fat deficiency, whereas in lungs, AHH and Cyt.c-reductase were decreased without any change in Cyt.P-450 level. In mice, feeding of fat-free diet did not cause any alteration in hepatic AHH and Cyt.P-450, but the levels of Cyt.b5 and Cyt.c-reductase were significantly reduced. In contrast to liver, Cyt.P-450 and Cyt.b5 were increased in lungs. Activity of UDPGT was lowered both in liver and lungs of rats whereas GST and GSH were increased in liver only. In mice, a decrease in UDPGT and appreciable increases in GST and GSH in liver were observed. However, in lungs, UDPGT activity was enhanced by feeding fat-free diet. These observations suggest that mice and rats respond differentially to the depletion of fat in the diet.

Animals↗
PubMed1990

Inhibition of arylhydrocarbon hydroxylase and cytochrome P-450 by 20-methylcholanthrene and phenobarbital in guinea pig on excessive doses of ascorbic acid.

Treatment of guinea pigs on adequate ascorbic acid (AA) with 20-methylcholanthrene (MCA) and phenobarbital (PB) significantly increased hepatic arylhydrocarbon hydroxylase (AHH), cytochrome P-450 and cytochrome-b5 activities. In lungs, only MCA treatment significantly enhanced the activities of AHH, cytochrome P-450 and cytochrome b5. In animals on excessive doses of AA, there was inhibition of hepatic AHH, cytochrome P-450 and cytochrome b5 levels by treatment with these xenobiotics. Also, inhibition was observed in pulmonary AHH and cytochrome P-450 levels. The relevance of these observations in excessive AA-fed guinea pigs to carcinogenesis requires further extensive investigations.

Animals↗
PubMed1988

Effect of cigarette smoke inhalation on antioxidant enzymes and lipid peroxidation in the rat.

Inhalation of cigarette smoke significantly increased glutathione (GSH) content and increased lipid peroxidation without altering the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) or glutathione reductase (GR) in the lung (six male Wistar rats). Following intratracheal administration of benzo[a]pyrene (BP), an increase in pulmonary GSH-Px activity, GSH content and lipid peroxidation was observed after 12 h. GSH-Px activity and GSH content returned to control values by 7 and 30 days, respectively, whereas lipid peroxidation in the lung remained significantly greater than the control value for up to 7 days of BP administration. Hepatic activity of SOD was increased significantly, whereas the activities of GSH-Px, catalase, GR, and GSH content were not changed by inhalation of cigarette smoke. On administration of BP, a significant increase in the activities of SOD and GSH-Px was observed at 12 h. After 7 and 30 days, the activities of these antioxidant enzymes were comparable to their respective control group values. No change in the activity of catalase or in the level of lipid peroxidation was noted throughout the entire study period.

Administration, Inhalation↗